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Introduction
Liver cancer poses a major challenge to global health, with hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) being the most common primary liver malignancies. These cancers rank among the seven leading causes of cancer-related deaths in both men and women, with an average 5-year survival rate of only 22%1. Additionally, metastases from other organs frequently affect the liver. The accurate intraoperative identification and discrimination of these tumor types are critical for effective surgical intervention and improved patient outcomes. Surgical tumor resections of HCC, CCC and liver metastases require a precise delineation of malignancy margins to reduce the risk of recurrent tumor growth while preserving as much healthy tissue as possible. This is particularly crucial regarding the infiltrative nature of liver tumors, which often extend beyond visible borders2.
Current state-of-the-art for the intraoperative assessment of tumor margins relies primarily on frozen section analysis. This technique involves rapid tissue freezing, sectioning, and histopathological evaluation. Although effective, limitations of this method are obvious. It depends on staining and labelling; it is time- and staff-consuming and of subjective fashion. However, error rates of frozen section analysis in hepato-pancreato-biliary histopathology compared to permanent, paraffin-embedded analysis are reported to be around 2%. Yet, most mistakes are made due to misinterpretation and lack of pathologist’s experience3, 4–5.
Hence, there is a pressing need for real-time, objective, and label-free methods that can assist surgeons in rapid and accurate discrimination between tumor entities during liver cancer surgery inside the operation room.
In recent years, molecular spectroscopy has emerged as a promising tool in cancer diagnostics due to its ability to provide detailed molecular information based on the characteristic molecular vibrations of tissue components6, 7, 8–9. In infrared (IR) spectroscopy, IR light interacts with the molecules in biological tissues, producing unique spectral fingerprints that correspond to specific molecular structures, such as proteins, lipids, carbohydrates, and nucleic acids. These fingerprints can be used to differentiate between normal and malignant tissues, as well as between various types of tumors9, 10–11. One of the key advantages of IR spectroscopy is its ability to perform these analyses without the need for tissue staining or preparation, making it ideal for intraoperative applications.
Recent advances in fiber-optic technology have enabled...